Abstract
The production, removal, and remodeling of fibrillar collagen is fundamental to mechanical homeostasis in arteries, including dynamic morphological and microstructural changes that occur in response to sustained changes in blood flow and pressure under physiological conditions. These dynamic processes involve complex, coupled biological, chemical, and mechanical mechanisms that are not completely understood. Nevertheless, recent simulations using constrained mixture models with phenomenologically motivated constitutive relations have proven able to predict salient features of the progression of certain vascular adaptations as well as disease processes. Collagen turnover is modeled, in part, via stress-dependent changes in collagen half-life, typically within the range of 10–70 days. By contrast, in this work we introduce a biochemomechanical approach to model the cellular synthesis of procollagen as well as its transition from an intermediate state of assembled microfibrils to mature cross-linked fibers, with mechano-regulated removal. The resulting model can simulate temporal changes in geometry, composition, and stress during early vascular adaptation (weeks to months) for modest changes in blood flow or pressure. It is shown that these simulations capture salient features from data presented in the literature from different animal models.
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Data availability
The main codes for the biochemomechanical model are accessible at https://github.com/baeksi/Biochemechanical-model-of-collagen-turnover. Additional data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank Dr. Vasilina Filonova for assisting in code development to improve simulation efficiency.
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This work was supported, in part, by the National Science Foundation (CMMI-1150376 to SB) and the National Institutes of Health (R01 HL105297 to JDH and U01 1HL135842 to SB).
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SB and JDH conceived the project. HGT developed the initial codes and performed simulations. HNM verified the initial simulations and extended their scope. HGT, SB and JDH wrote the manuscript, and HNM edited it.
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Tilahun, H.G., Mullagura, H.N., Humphrey, J.D. et al. A biochemomechanical model of collagen turnover in arterial adaptations to hemodynamic loading. Biomech Model Mechanobiol 22, 2063–2082 (2023). https://doi.org/10.1007/s10237-023-01750-1
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DOI: https://doi.org/10.1007/s10237-023-01750-1